Pancreatic Lymphoma Research Articles

1423 Primary B-Cell Pancreatic Lymphoma Presenting as Acute Pancreatitis

INTRODUCTION: Primary pancreatic lymphoma (PLL) is a very rare type of pancreatic malignancy and accounts for less than 1% of all pancreatic masses. Presenting symptoms are non-specific and may lead to delay in diagnosis. CASE DESCRIPTION/METHODS: A 71-year-old man with diabetes mellitus and hypertension presented to hospital with epigastric pain, nausea, and vomiting for 3 days. He had loss of appetite and weight loss for 2 months. On physical examination, his vital signs were normal, and he had tenderness on palpation at epigastric area without signs of peritonitis. Complete blood counts were within normal limits. He had transaminitis and elevated total bilirubin and alkaline phosphatase. Serum amylase and lipase were 123 IU/L (normal: 13-53) and 864 IU/L (normal: 13-60), respectively. Tumor markers, including CA 19.9 and CEA, were normal. Magnetic resonance imaging (MRI) of the pancreas showed a large mass at the pancreatic head measuring 8.3 × 7.6 cm in maximum diameter with peripancreatic and retroperitoneal adenopathy (Figure 1). Endoscopic ultrasound demonstrated the mass in the pancreatic head and malignant-appearing peripancreatic lymph nodes. Computer tomography (CT) guided biopsy of the pancreatic mass was performed. Pathology revealed a high grade B-Cell Lymphoma. Bone marrow biopsy did not show atypical cells. Staging CT scans revealed a 9 mm sized mediastinal node. He was diagnosed with stage III high grade B-Cell primary pancreatic lymphoma. An International Prognostic Index was 2 which predicts a 5-year survival of 51%. He received R-CHOP regimen for treatment and currently on cycle 5 with a good response. DISCUSSION: Primary pancreatic lymphoma is a rare malignancy accounting for 0.7% of all pancreatic malignancies and 1% of extranodal lymphomas. The disease is male predominant about 7 times more frequent than in females.2 Non-specific gastrointestinal symptoms are the most common presentations, including abdominal pain, obstructive jaundice, or acute pancreatitis. Imaging of the pancreas by MRI or CT scan may help to distinguish PPL from the more common pancreatic adenocarcinoma. However, cytohistology of the mass is required for diagnosis and to guide definitive treatment. Surgery has a limited role in management, and chemotherapy is the main treatment.

1416 Rare Presentation of Large Pancreatic Mass With Chylous Ascites

INTRODUCTION: Primary pancreatic lymphomas (PPL) are very rare and mimic pancreatic head cancer. We present a case of a man who presented with a pancreatic mass and chylous ascites, and was found to have PPL. CASE DESCRIPTION/METHODS: A 69-year-old man presented with 2 months of anorexia, abdominal pain and distension. He denied fever, chills or weight loss. Abdomen was distended, soft, non-tender with shifting dullness and fluid thrill. Laboratory tests were noncontributory except for mildly elevated LDH 254 U/L. Abdominal computed tomography (CT) showed a 20 × 10 × 17 cm soft tissue mass impinging the distal duodenum, replacing the proximal pancreatic parenchyma, encasing the celiac and superior mesenteric arteries; ascites, lymphadenopathy and multiple omental nodules were seen. No cirrhosis or hepatomegaly noted. 2.5 L of grossly chylous fluid was drained with lymphocytic predominance, high triglycerides 980 mg/dL and negative cytology. Endoscopic ultrasound (EUS) showed an irregular hypoechoic mass. Fine needle aspiration (FNA) showed lymphoid cells with irregular nuclear membrane contours strongly positive for CD20, consistent with B cell lymphoma. PET-CT scan confirmed a metabolically active pancreatic mass with inguinal, aortocaval, juxtadiaphrgamatic and inframammary lymphadenopathy. Diagnostic laparoscopic biopsy confirmed diffuse B-cell lymphoma of germinal center origin positive for CD10, BCL6, BCL2 and CD45. Patient received 6 cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) which he tolerated well. Follow-up PET CT scan showed reduction in size of pancreatic mass and lymph nodes without areas of new/worsening lymphoma. DISCUSSION: PPLs comprise 0.5% of all pancreatic masses. Diagnostic criteria include dominant pancreatic mass, without superficial or mediastinal lymphadenopathy, absent hepatosplenic involvement and a normal blood leukocyte count. Clinical presentation is non-specific without classic symptoms of nodal lymphoma. Abdominal pain is the most common symptom (83%), followed by abdominal mass and weight loss. High tumor burden, β2-microglobulin levels >2 mg/l and high LDH levels are poor prognostic markers. Definitive diagnosis requires histologic confirmation, EUS-guided sampling is highly accurate. Treatment options include surgery, chemotherapy, radiation, alone or in combination. Cure rates upto 30% have been reported. Long term remission can be obtained with CHOP chemotherapy alone in majority of patients. Addition of rituximab results in overall improvement in patient survival.

1415 A Rare Presentation of Diffuse Large B-Cell Lymphoma as a Pancreatic Mass

INTRODUCTION: Diffuse Large B-Cell Lymphoma (DLBCL) of Pancreas is a fast-growing Non-Hodgkin lymphoma (NHL), which accounts for only 0.5% of all pancreatic tumors. In most cases, it presents as a single, metastatic mass or diffuse nodules in the pancreas. DLBCL should be considered in patients with a pancreatic mass, especially if: personal history of lymphoma, presence of an immunodeficiency syndrome, or prior infection with EBV. CASE DESCRIPTION/METHODS: A 60-year-old type II diabetic male presented to the ED with nausea, vomiting, diarrhea and 40 lb weight loss. Patient's mother had known pancreatic adenocarcinoma. Social history revealed multiple sexual partners of both sexes. On exam patient had epigastric tenderness, and a 1 cm non-tender supraclavicular lymph node. A CT abdomen/pelvis with contrast revealed a 4.8 × 7.5 × 4 cm mass in the head of the pancreas and retroperitoneal metastatic adenopathy. Endoscopic ultrasound characterized a “U” shaped parenchymal mass extending from the head to the tail of the pancreas encircling the splenic artery. Fine needle aspiration and biopsy both revealed DLBCL. Bone marrow biopsy and imaging studies were unremarkable, therefore the pancreas was determined to be the primary site. Additional testing found the patient to be HIV positive with a CD4 count of 119 and thus diagnosed with AIDS. He was started on antiretroviral therapy prior to initiation of R-CHOP (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine and Prednisone). Following his first chemotherapy dose, he was readmitted to the hospital with fever and weakness. Patient continued to decompensate and expired 23 days from his initial diagnosis. DISCUSSION: Most common sites of extranodal involvement of NHL are the gastrointestinal tract, liver, lung, bone marrow, and the central nervous system. DLBCL can present with extra-nodal involvement in about 50% of cases, but only 0.2-2% involve the pancreas. Clinically, most cases of Primary Pancreatic Lymphoma (PPL) are misdiagnosed as pancreatic adenocarcinoma. PPL generally carries a better prognosis once treatment is initiated in an immunocompetent individual. In this rare case, the patient was concurrently diagnosed with AIDS and Stage IV DLBCL of the pancreas. This case highlights an unusual presentation of a primary pancreatic malignancy that typically presents as a metastatic lesion. Furthermore, this case shows the utility of endoscopic ultrasound to better identify and characterize pancreatic masses when compared to other diagnostic modalities.

The Computed Tomography "Sandwich Sign" for Primary Pancreatic Lymphoma.

The Computed Tomography "Sandwich Sign" for Primary Pancreatic Lymphoma.

DNA-Methylation-Caused Downregulation of miR-30 Contributes to the High Expression of XPO1 and the Aggressive Growth of Tumors in Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma is one of the most aggressive cancers, with high mortality in the United States. One of the important signal transduction proteins involved in the regulation of pancreatic cancer’s aggressive progression is the nuclear export protein (XPO1). High expression of XPO1 has been found in pancreatic, lung, breast and other cancers and lymphomas with a poor prognosis of patients with tumors and high proliferative activity of cancer cells. Because XPO1 exports multiple tumor suppressor proteins simultaneously from the nucleus, the inhibition of XPO1 may retain multiple tumor suppressors in the nucleus, resulting in the suppression of cell proliferation and the induction of apoptosis in tumors. In this study, we found that the high expression of XPO1 in pancreatic cancer cells could be, in part, due to the methylation of the miR-30 gene, leading to the low expression level of the miR-30 family. By co-transfection of the XPO1 3′-UTR-Luc target vector with miR-30 mimic, we found that XPO1 is a direct target of the miR-30 family. We also observed that the enforced expression of the miR-30 family inhibited the expression of XPO1, resulting in the suppression of pancreatic cancer growth both in vitro and in vivo. These findings could help to design a novel therapeutic strategy for the treatment of pancreatic cancer by introducing miR-30 into cancer cells.

Metformin Associated With Increased Survival in Type 2 Diabetes Patients With Pancreatic Cancer and Lymphoma

BackgroundThe biguanide drug metformin is one of the most commonly used medications for the treatment of type 2 diabetes mellitus. Diabetics are at an increased risk for cancer. Previous studies have demonstrated improved outcomes in patients taking metformin suffering from prostate, colon, lung, thyroid, and esophageal cancers. Metformin's main antineoplastic mechanism of action is thought to be mediated through inhibition of mammalian target of rapamycin, inhibition of hypoxia-inducible factor 1 (HIF-1) alpha, and activation of p53. We investigated the overall survival of type 2 diabetic patients on metformin with pancreatic cancer and lymphoma using the Computerized Patient Record System at the Veterans Affairs Medical Center, Memphis TN. MethodsLymphoma and pancreatic cancer patients with type 2 diabetes were sorted into an experimental (metformin) group and a control (nonmetformin) group. Patients were compared on baseline characteristics including race, body mass index, and age. Cancer outcomes including overall survival, metastasis, recurrences, and incidence of new malignancies were recorded. Hemoglobin A1C, creatinine and cancer treatment modalities were recorded and compared. Statistical analyses used included unpaired t tests and Chi-squared tests. ResultsThere was significantly greater overall long-term survival in the metformin group compared to the nonmetformin group for lymphoma (5.89 vs 1.29 years, P < 0.001) and for pancreatic cancer (0.68 vs 0.22 years, P = 0.016). Cancer treatment modalities in both groups were comparable. ConclusionsMetformin is associated with a significant, positive effect of increased overall survival in type 2 diabetes patients with pancreatic cancer and lymphoma. These results are encouraging, and prospective studies should be done to further investigate metformin's effects in cancer.

Epidemiology, Tumor Characteristics, and Survival in Patients With Primary Pancreatic Lymphoma: A Large Population-based Study Using the SEER Database.

Primary pancreatic lymphoma (PPL) is an extranodal manifestation of non-Hodgkin lymphoma originating in the pancreas, which constitutes <1% of all pancreatic neoplasms. Because of the rarity of the disease, most data on PPL are derived from case reports and small case series. To provide better insight into the epidemiology, treatment, and outcomes of these patients, we conducted an analysis of patients with PPL from the Surveillance, Epidemiology and End Results (SEER) database, which is presented in this study. Patients with PPL were identified using the International Classification of Disease for Oncology, third edition histology codes for lymphoma (9590/3-9734/3), with pancreas (C25.0-C25.9) listed as the primary disease site. We collected data on patient demographics, year of diagnosis, primary tumor site, histology, first line of treatment received, and survival until death or last follow-up for the period 1973-2014. Overall, 835 patients were included. The median (range) age of the study population was 67 (2 to 98) years. The median (95% confidence interval) overall survival for the cohort was 53 (37 to 73) months. On univariable analyses, age, stage, and use of chemotherapy were statistically associated with improved overall survival. Besides these factors, white race was associated with improved cause-specific survival on multivariable analysis. This large population-based series describes PPL in detail. Younger age, white race, early stage, and initial treatment with chemotherapy are associated with improved survival in patients with PPL.

Pylorus-preserving Pancreaticoduodenectomy with Reconstruction of Portal Vein for Primary Pancreatic Lymphoma: One Case Report

Primary pancreatic lymphoma is a rare disease. It is insidious, always no specific symptoms and signs, and easy to be misdiagnosed as pancreatic carcinoma. Now 1 case of primary pancreatic lymphoma is reported in our hospital for sharing.

Arterial thromboembolic events preceding the diagnosis of cancer in older persons

AbstractCancer patients face an increased risk of arterial thromboembolism; however, it is uncertain when this excess risk begins. This study evaluated the risk of arterial thromboembolism before cancer diagnosis. Using the population-based Surveillance Epidemiology and End Results-Medicare linked dataset, we identified 374 331 patients ≥67 years of age with a new primary diagnosis of breast, lung, prostate, colorectal, bladder, uterine, pancreatic, gastric cancer, or non-Hodgkin lymphoma from 2005 through 2013. Cancer patients were individually matched by demographics and comorbidities to Medicare beneficiaries without cancer, who served as controls. Validated diagnosis codes were used to identify arterial thromboembolic events, defined as a composite of myocardial infarction or ischemic stroke. The Mantel-Haenszel estimator was used to compare risks of arterial thromboembolic events between cancer and noncancer groups during 30-day periods in the 360 days before date of cancer diagnosis. From 360 to 151 days before cancer diagnosis, the 30-day interval risks of arterial thromboembolic events were similar between cancer patients and matched controls. From 150 to 1 day before cancer diagnosis, the interval 30-day risks of arterial thromboembolic events were higher in cancer patients vs matched controls, progressively increasing as the cancer diagnosis date approached and peaking during the 30 days immediately before cancer diagnosis, when 2313 (0.62%) cancer patients were diagnosed with an arterial thromboembolic event vs 413 (0.11%) controls (odds ratio, 5.63; 95% confidence interval, 5.07-6.25). In conclusion, the risk of arterial thromboembolic events begins to increase 150 days before the date of cancer diagnosis in older persons and peaks in the 30 days before.

Pancreatic Neuroendocrine Tumor, Lymphoma, and Squamous Cell Carcinoma of Larynx; Three Primary Cancers in One Patient: A Case Report

Pancreatic Neuroendocrine Tumor, Lymphoma, and Squamous Cell Carcinoma of Larynx; Three Primary Cancers in One Patient: A Case Report

CA242 as a biomarker for pancreatic cancer and other diseases.

CA242 is a sialic acid-containing carbohydrate antigen attached to core proteins/lipids detected on the cell surface or in serum. Increased serum levels of CA242 have been used clinically as diagnostic biomarkers for pancreatic, colorectal, and other cancers. Since CA242 is overexpressed in malignant tumor tissues compared to that in normal tissues, it is believed that serum CA242 is a product of cancer cells. Thus far, the serum CA242 levels in patients suffering from different types of cancer and noncancerous diseases have not been systematically compared. In our current study, we acquired data of serum CA242 levels from 34,680 patients with 27 clinically defined diseases and from healthy controls (1317) in the clinical laboratory of our hospital over the past 5 years. The mean, median, and -log10p values were calculated. Our data showed that patients with pancreatic cancer, cervical cancer, and lymphoma had the highest median values of serum CA242, which were followed by esophagus cancer, colon cancer, ovarian cancer, type 2 diabetes mellitus, rectal cancer, coronary heart disease, breast cancer, diabetic nephropathy, acute myocardial infarction, and 15 other types of diseases compared to that of healthy controls. In contrast, patients suffering from sequela of brain damage and anemia had statistically lower median values than healthy controls. Based on the -log10p values, the increased serum CA242 levels could be used not only for diagnosis of pancreatic and other cancers, but also for diagnosis of type 2 diabetes mellitus and coronary heart disease, suggesting CA242 might be a systemic malfunction biomarker associated with cancers and other chronic diseases.

Protective effects of either C-peptide or l-arginine on pancreatic β-cell function, proliferation, and oxidative stress in streptozotocin-induced diabetic rats.

Diabetes and cardiometabolic risk factors including hypertension and dyslipidemia are the major threats to human health in the 21st century. Apoptosis in pancreatic tissue is one of the major causes of diabetes type 1 progression. The aim of this study was to investigate the effects of C-peptide or l-arginine on some cardiometabolic risk factors, pancreatic morphology, function and apoptosis, and the mechanisms of their actions. Forty adult male albino rats were divided into four equal groups: 1-control nondiabetic, 2-diabetic (no treatment), 3-diabetic + C-peptide, and 4-diabetic + l-arginine. Diabetes was induced by a single intraperitoneal injection of high dose streptozotocin. At the end of the experiment, sera glucose, insulin levels, total antioxidant capacity (TAC), malondialdehyde (MDA), nitric oxide (NO), and pancreatic MDA, TAC, and B-cell lymphoma 2 were measured. The morphology and proliferating activity of the pancreas were examined by hematoxylin and eosin histological stain, proliferative cell nuclear antigen (PCNA), and insulin antibodies. Our results showed that induction of diabetes caused hyperglycemia, dyslipidemia, and oxidative stress. However, administration of C-peptide or l-arginine significantly improved the pancreatic histopathology with a significant increase in the area % of insulin immunoreactivity, the number of PCNA immunopositive cells, the number of islets, and the diameter of islets compared with the diabetic group. C-peptide treatment of the diabetic rats completely corrected these errors, while l-arginine partially antagonized the above diabetic complications. So the administration of C-peptide as an adjuvant therapy in type 1 diabetes can significantly decrease apoptosis of pancreas and subsequent progression of diabetes complication.

Combined HDAC and BET Inhibition Enhances Melanoma Vaccine Immunogenicity and Efficacy.

The combined inhibition of histone deacetylases (HDAC) and the proteins of the bromodomain and extraterminal (BET) family have recently shown therapeutic efficacy against melanoma, pancreatic ductal adenocarcinoma, testicular, and lymphoma cancers in murine studies. However, in such studies, the role of the immune system in therapeutically controlling these cancers has not been explored. We sought to investigate the effect of the HDAC inhibitor romidepsin (RMD) and the BET inhibitor IBET151, both singly and in combination, on vaccine-elicited immune responses. C57BL/6 mice were immunized with differing vaccine systems (adenoviral, protein) in prime-boost regimens under treatment with RMD, IBET151, or RMD+IBET151. The combined administration of RMD+IBET151 during vaccination resulted in a significant increase in the frequency and number of Ag-specific CD8+ T cells. RMD+IBET151 treatment significantly increased the frequency of vaccine-elicited IFN-γ+ splenic CD8+ T cells and conferred superior therapeutic and prophylactic protection against B16-OVA melanoma. RNA sequencing analyses revealed strong transcriptional similarity between RMD+IBET151 and untreated Ag-specific CD8+ T cells except in apoptosis and IL-6 signaling-related genes that were differentially expressed. Serum IL-6 was significantly increased in vivo following RMD+IBET151 treatment, with recombinant IL-6 administration replicating the effect of RMD+IBET151 treatment on vaccine-elicited CD8+ T cell responses. IL-6 sufficiency for protection was not assessed. Combined HDAC and BET inhibition resulted in greater vaccine-elicited CD8+ T cell responses and enhanced therapeutic and prophylactic protection against B16-OVA melanoma. Increased IL-6 production and the differential expression of pro- and anti-apoptotic genes following RMD+IBET151 treatment are likely contributors to the enhanced cancer vaccine responses.

Two-dimensional Texture Analysis Based on CT Images to Differentiate Pancreatic Lymphoma and Pancreatic Adenocarcinoma: A Preliminary Study

To retrospectively assess the diagnostic performance of texture analysis and characteristics of CT images for the discrimination of pancreatic lymphoma (PL) from pancreatic adenocarcinoma (PA). Fifteen patients with pathologically proved PL were compared with 30 age-matched controls with PA in a 1:2 ratio. Patients underwent a CT scan with three phases including the precontrast phase, the arterial phase, and the portal vein phase. The regions of interest of PA and PL were drawn and analyzed to derive texture parameters with MaZda software. Texture features and CT characteristics were selected for the discrimination of PA and PL by the least absolute shrinkage and selection operator and logistic regression analysis. Receiver operating characteristic analysis was performed to assess the diagnostic performance of texture analysis and characteristics of CT images. Sixty texture features were obtained by MaZda. Of these, four texture features were selected by least absolute shrinkage and selection operator. Following this, three texture features and nine CT characteristics were excluded by logistic regression analysis. Finally, "S(5, -5)SumAverg" (texture feature) and "Size" (CT characteristic) were selected for the receiver operating characteristic analysis. The AUC of "S(5, -5)SumAverg" and "Size" were to be 0.704 and 0.821, respectively, with no significance between them (p = 0.3064). Two-dimensional texture analysis is a quantitative method for differential diagnosis of PL from PA. The diagnostic performance of both texture analysis and CT characteristics was similar.

Abstract 4861: Initial preclinical evaluation of a novel inhibitor of mitochondrial metabolism against prostate cancer

Abstract CPI-613 is a novel inhibitor of mitochondrial metabolism that has recently shown promise in early stage clinical trials for pancreatic cancer, lymphoma, and leukemia. It is a lipoate analogue that selectively inhibits pyruvate dehydrogenase (PDH) and alpha-ketoglutarate dehydrogenase (KGDH) complexes in tumor cells (reviewed in Exp.Rev.Clin.Pharma. 7, 837). Since these two enzymes control the vast majority of carbon flow into the tricarboxylic acid (TCA) cycle, CPI-613 significantly inhibits mitochondrial metabolism. Importantly, it has demonstrated a favorable safety profile in clinical trials, presumably due to its documented selectivity to cancer metabolism. Early phase clinical trials with CPI-613 have demonstrated very promising clinical responses in pancreatic cancer, leukemia, and lymphoma when used in combination with standard chemotherapy. For example, in a recently published Phase I clinical trial in 18 patients with Stage 4 pancreatic cancer in combination with a modified FOLFIRINOX regiment, three (17%) had a complete response, eight (44%) had a partial response, three (17%) had stable disease, and four (22%) had progressive disease. Since altered cancer metabolism is a hallmark of cancer in general, we hypothesized that CPI-613 should have efficacy in other cancers, including prostate cancer, which is the second most common malignancy in men that affects over 160,000 men in the U.S annually. To test our hypothesis, we treated prostate cancer cell lines with CPI-613 in vitro and in vivo in a preclinical murine flank model. We found that CPI-613 was highly effective at killing prostate cancer cells in vitro, which was similar to its previously published potency in pancreatic cancer cells. Furthermore, we found in vitro therapeutic synergy with docotaxel, a standard of care treatment of advanced prostate cancer. We therefore tested CPI-613 in a preclinical Pc-3 flank model of androgen-resistant prostate cancer. Groups of mice (n=8) were treated 2-3 times per a week for 5 weeks with 2.5mg/kg of CPI-613, 10mg/kg of CPI-613 and control saline after tumors reached approximately 40mm3. CPI-613 was formulated in the same manner as it was for clinical trials. Both groups of mice treated with CPI-613 demonstrated a significant decrease in tumor growth without any toxicity. There was no observed difference between doses, which may be due to having crossed the threshold of drug uptake and concentration required in the mitochondria for a response. Furthermore, there was a significant increase in survival between treated groups and the control group, again without a dose effect. These results for the first time indicate biological activity of CPI-613 both in vitro and in vivo against prostate cancer and therefore warrants further investigation in representative preclinical prostate cancer models and in combination with standard-of-care therapies. Citation Format: Kiran K. Solingapuram Sai, Anirudh Sattiraju, Zuzana Zachar, Michael S. Dahan, Robert Shorr, Timothy S. Pardee, Paul M. Bingham, Akiva Mintz. Initial preclinical evaluation of a novel inhibitor of mitochondrial metabolism against prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4861.

Abstract 2874: Benzaldehyde inhibits the multiple signals in cancer by suppressing the binding activity of overexpressed 14-3-3ζ and represses the pRb/E2F transcriptional pathway

Abstract Benzaldehyde (BA) is the simplest aromatic aldehyde composed of only benzene ring and aldehyde. It is constituents of many fruits and flavor essence. Anti-cancer effect of BA was first reported in 1980, and multi institutional clinical trials by using derivatives of BA were performed in 1980's in Japan. However, clinical study was aborted due to the policy and strategic change in the company. Only the safety of the compound was confirmed. Given that we had multiple effective clinical cases including pancreatic cancers and chemo-resistant non Hodgkin lymphoma, we attempted to elucidate the mechanism of anti-cancer effect of BA. We have previously reported that BA inhibits cancer-related multiple pathways such as PI3K/AKT/mTOR, STAT3, NFκB and ERK, leading to cell death and growth suppression in BA sensitive pancreatic cancer cell line BxPC3, but not in normal cells. We found that such mechanism is based on the BA-mediated inhibition of 14-3-3ζ binding to its client proteins. To further analyze the BA-mediated regulation of 14-3-3ζ, we generated HEK293 cells overexpressing 14-3-3ζ and confirmed that BA suppressed mTOR pathway in the 14-3-3ζ expressing HEK293 cells but not in parental HEK293 cells. Furthermore, we found that depletion of 14-3-3ζ suppresses mTOR signal in BxPC3 and BA-induced reduction of phosphorylation of mTOR signal proteins. Moreover, we performed microarray analysis on three pancreatic cancer cell lines (BxPC-3, AsPC1, PANC1) and found that stress response genes were upregulated in BxPC-3 cells by BA treatment. E2F2 and E2F targeted genes and histone cluster genes in 6p22 were suppressed in not only BxPC-3 but also BA low-sensitive PANC1. We confirmed that BA treatment suppresses the expression of E2F2 and E2F target genes. Of note, protein levels of pRb and cyclin D were also suppressed by BA treatment. Those data suggest that BA inhibits overexpressed 14-3-3ζ mediated multiple signaling pathway and consequently represses pRB/E2F and E2F target genes, resulting in inhibition of cell cycle progression, DNA replication and DNA repair. We propose that those mechanisms can explain why this safe compound is effective for refractory cancers. Citation Format: Jun Saitoh, Hideyuki Saya. Benzaldehyde inhibits the multiple signals in cancer by suppressing the binding activity of overexpressed 14-3-3ζ and represses the pRb/E2F transcriptional pathway [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2874.

Portal vein pseudoaneurysm secondary to pancreatic lymphoma and biliary stent insertion: a rare cause of haemobilia

BackgroundHaemobilia, defined as bleeding from the biliary tree, is a rare entity. The most common cause of haemobilia is iatrogenic trauma, which accounts for 70% of cases. Pseudoaneurysms of the portal vein are an extremely rare cause of haemobilia with only four reported cases to date. Conservative treatment, open surgical repair and percutaneous trans hepatic stent-grafting have all been employed in these cases. This displays the lack of consensus regarding the treatment of this condition.We report the first case of a portal vein pseudoaneurysm following endoscopic common bile duct stent placement performed to relieve obstruction of the common bile duct for lymphomatous infiltration of the pancreatic head. The pseudoaneurysm was successfully treated by placement of a percutaneous trans hepatic covered stent-graft.Case presentationA 42-year-old man with a history of lymphomatous infiltration of the pancreatic head and recent endoscopic common bile duct stent placement presented with sudden onset large volume haematemesis. On the portal venous phase of a triple phase CT, this was found to be secondary to a portal vein pseudoaneurysm bulging into the upper portion of the indwelling biliary stent. The pseudoaneurysm was successfully treated by percutaneous trans hepatic placement of a covered vascular stent-graft.ConclusionsWe report a rare case of portal vein pseudo aneurysm successfully treated by percutaneous trans hepatic portal venous covered vascular stent-graft insertion.

CT imaging of primary pancreatic lymphoma: experience from three referral centres for pancreatic diseases

PurposeTo describe CT characteristics of primary pancreatic lymphoma (PPL), a rare disease with features in common with adenocarcinoma.Materials and methodsFourteen patients were enrolled. CT: unenhanced scan, contrast-enhanced pancreatic and venous phases. Image analysis: tumour location; peri-pancreatic vessel encasement; necrosis; enlarged lymph nodes; fat stranding; enlarged bile duct and pancreatic duct; neoplasm longest dimension, volume and density.ResultsHistopathological diagnoses: follicular non-Hodgkin lymphoma (5/14), diffuse large B-cell lymphoma (6/14) and high-grade B-cell lymphoma not otherwise specified (3/14). Six of 14 PPLs were located in the pancreatic head and 7/14 in the body-tail; 1/14 involved the whole gland. In 5/14 cases the superior mesenteric artery and vein were encased; splenic vein and artery encasement was depicted in 2 PPLs. Necrosis was present in 2/14. Enlarged retroperitoneal lymph nodes were found in 11 cases and fat stranding in all patients. The bile duct was dilated in six cases and the pancreatic duct in five. Mean neoplasm longest diameter and volume were 8.05 cm and 210.8 cm3. Mean tumour attenuation values were 39.1 HU at baseline, 60.6 HU in the pancreatic phase and 71.4 HU in the venous phase.ConclusionsPPL presents as a large mass lesion with delayed homogeneous enhancement; peri-pancreatic fat stranding and vessel encasement are present, without vascular infiltration. Pancreatic duct dilatation is rare.Key points• Primary pancreatic lymphoma (PPL) is a rare haematological disease• PPL presents imaging features in common with pancreatic carcinoma but also some distinctive findings• The majority of PPLs are large lesions with delayed homogeneous enhancement• Peri-pancreatic fat stranding and vessel encasement are common in PPL• Vascular infiltration and pancreatic duct dilatation are rare in PPL

Primary Pancreatic Burkitt’s Lymphoma: A Case Report and Review of the Literature

Primary pancreatic lymphoma (PPL) is of very rare occurrence as an extra nodal site of Non-Hodgkin's lymphoma (NHL). It represents less than 1% of NHL. Out of which Burkitt lymphoma of pancreas is of a rare presentation. It usually occurs in children and presenting in adults is uncommon. The prevalence of pancreatic Burkitt lymphoma is not known as the incidence is significantly low. Clinical features of PPL are predominantly nonspecific and can become difficult with associated inflammation of pancreas. Differentiation of lymphoma to adenocarcinoma is important as chemotherapy is the main stay of treatment in lymphoma. We report a case of 68-year-old female who presented with nonspecific symptoms and was found to have obstructive jaundice secondary to pancreatic head neoplasm which was proved to be pancreatic Burkitt lymphoma which is a rare presentation.

Pediatric pancreatic Burkitt lymphoma with obstructive jaundice: case report of a six-year-old child

Introduction: Burkitt lymphoma represents about 50% of non-Hodgkin lymphomas and 3% of cancers in children. It commonly affects the abdomen; however, pancreatitis is a very rare initial presentation. Less than 10 cases with this presentation are reported in the literature. Observation: We report the case of a six-year-old girl who presented a rapidly progressing obstructive jaundice evolving for a week. The LDH rate was not increased. Medical imaging has shown a global increase in the size of the pancreas, homogeneous hepatomegaly with dilatation of the gallbladder and the intra-hepatic bile ducts, and infiltration of the left ovary, without ascites. The patient was diagnosed with pancreatic Burkitt Lymphoma after an endoscopic exploration and tumor biopsy. Conclusion: While extremely rare, Burkitt lymphoma should be evoked in the case of pancreatitis with a global increase of the pancreas size, associated with other intra-abdominal organ infiltration in the pediatric population.